Despite evidence for familial patterns of transmission and recent studies of anxiety and depression in children, the relationship between the child and adult disorders has not been systematically or prospectively investigated. The purpose of this longitudinal cross-sectional study is to identify a cohort of children who are at significant risk for the development of anxiety disorders. The study will identify critical psychological and biological factors leading to the development of anxiety disorders in children and adults. The benefits of a combined longitudinal, cross-sectional approach include the ability to conduct intermediate analyses to further the elaboration and refinement of hypotheses. Study results already confirm two initial hypotheses that both clinical disturbance and frequency of anxiety disorders are significantly increased in children of anxiety disordered adults; however, they also show an increased incidence of depression in these children. This confounding of anxiety and depression has impaired precise diagnosis, early identification and prevention efforts, and specification of etiology and pathological processes in many studies. We are studying children of anxious and depressed patients concurrently to facilitate differentiation of these disorders. Our experience indicates the need to improve the existing clinical instruments and to develop better measures to characterize and quantify the symptomatology of these disorders. Since we are primarily interested in identifying children at risk for significant adult disorders, the longitudinal cross-sectional design and multimodal methodology allows for repeated examination of a well-characterized population with new and improved measures, to further define enduring, persistent vulnerability traits and to study the natural history of these disorders. Study children are expected to show evidence of more definitive adult disorders over time. To differentiate anxiety from depression and other diagnoses such as attention deficit disorder, we are adding teacher measures and neuropsychological testing. In collaboration with the Departments of Genetics and Statistics, we are beginning an investigation of pedigree analysis which should lead to more intensive pedigree studies and eventually chromosomal studies such as restriction fragment analysis. The final outcome should provide significant analytic power to identify critical predictive factors.